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Na Sun

Publications and source records attributed to Na Sun.

10 recordsLinked to original sources
PubMed2026

Plasma Multiomics Links Early-Life Adversity to Disease and Cardiometabolic Health: A Population-Based Cohort Study.

BACKGROUND: Childhood adversity (CA) is associated with increased cardiovascular and cardiometabolic risk, but the molecular mechanisms remain unclear. We aimed to identify CA-related metabolomic and proteomic signatures and evaluate their roles in linking CA to incident diseases. METHODS: This prospective cohort study included 153 225 participants aged 48 to 64 years. CA was assessed using the Childhood Trauma Screener-5, capturing cumulative (0-5 domains) and individual adversity exposures. Plasma metabolomics and proteomics data were integrated to derive CA-related molecular signatures. Cox proportional hazards model was used to evaluate associations between CA, molecular signatures, and 58 incident diseases and mortality. Mediation analyses quantified the role of multiomics signatures. RESULTS: Each additional CA domain was associated with higher risk of 49 of 58 incident diseases (hazard ratios [HRs], 1.024-1.338) and a 7.3% higher all-cause mortality risk. Focusing on cardiometabolic health, the CA-related metabolic and proteomic signatures were independently associated with incident disease. Per 1-SD increase in the cumulative CA metabolic signature, the highest observed HR was 1.313 (95% CI, 1.278-1.349) for incident diabetes, and the risk for hypertension was also increased (HR, 1.136 95% CI, 1.114-1.159). Similarly, the proteomic signature was strongly associated with incident diabetes (HR, 1.645 95% CI, 1.489-1.818) and hypertension (HR, 1.223 95% CI, 1.155-1.295). The cumulative CA metabolic and proteomic signatures mediated up to 25.5% and 46.8% of the association with hypertension, respectively. CONCLUSIONS: CA is associated with a broad spectrum of diseases and mortality, with particularly strong links to cardiometabolic health. Multiomics signatures partially mediated these associations.

Humans↗
PubMed2006

Proteomics analysis of Thermoplasma acidophilum with a focus on protein complexes.

Two-dimensional gel electrophoresis (2DE) and MALDI-TOF MS were used to obtain a global view of the cytoplasmic proteins expressed by Thermoplasma acidophilum. In addition, glycerol gradient ultracentrifugation coupled to 2DE-MALDI-TOF MS analysis was used to identify subunits of macromolecular complexes. With the 2DE proteomics approach, over 900 spots were resolved of which 271 proteins were identified. A significant number of these form macromolecular complexes, among them the ribosome, proteasome, and thermosome, which are expressed at high levels. In the glycerol gradient heavy fractions, 10 as yet uncharacterized proteins (besides the well known ribosomal subunits, translation initiation factor eIF-6-related protein, elongation factor 1, and DNA-dependent RNA polymerase) were identified that are putative building blocks of protein complexes. These proteins belong to the categories of hypothetical or conserved hypothetical proteins, and they are present in the cytosol at low concentrations. Although these proteins exhibit homology to known sequences, their structures, subunit compositions, and biological functions are not yet known.

Archaeal Proteins↗
PubMed2006

A histidine/tryptophan pi-stacking interaction stabilizes the heme-independent folding core of microsomal apocytochrome b5 relative to that of mitochondrial apocytochrome b5.

The outer mitochondrial membrane isoform of mammalian cytochrome b5 (OM b5) is considerably more stable than its microsomal counterpart (Mc b5), whereas the corresponding apoproteins (OM and Mc apo-b5) exhibit similar stability. OM and Mc apo-b5 are also similar in that their empty heme-binding pockets (core 1) are highly disordered but that the remainder of each apoprotein (core 2) displays substantial hololike structure. Core 1 residue 71 is leucine in all known mammalian OM b5's and serine in the corresponding Mc proteins. Replacing Leu-71 in rat OM (rOM) b5 with Ser has been shown to (1) decrease apoprotein thermodynamic stability by >2 kcal/mol and (2) extend conformational disorder beyond core 1 and into core 2, as evidenced in part by loss of a near-UV circular dichroism signal associated with the side chain of invariant residue Trp-22. Herein we report identification of a conserved Mc b5 core 2 packing motif that plays a key role in stabilizing apoprotein conformation in the vicinity of Trp-22, thereby compensating for the presence of Ser at position 71: a pi-stacking interaction between the side chains of Trp-22 and His-15 that is extended by hydrogen bonding between the side chains of His-15, Ser-20, and Glu-11. The corresponding conserved packing motif in OM b5's differs in having arginine at position 15 and glutamate at position 20. We also present evidence indicating that the conserved Mc b5 packing motif noted above contributes to the unusually extensive secondary structure exhibited by bovine Mc apo-b5 in the urea-denatured state.

Animals↗
PubMed2006

Streptococcus suis sequence type 7 outbreak, Sichuan, China.

An outbreak of Streptococcus suis serotype 2 emerged in the summer of 2005 in Sichuan Province, and sporadic infections occurred in 4 additional provinces of China. In total, 99 S. suis strains were isolated and analyzed in this study: 88 isolates from human patients and 11 from diseased pigs. We defined 98 of 99 isolates as pulse type I by using pulsed-field gel electrophoresis analysis of SmaI-digested chromosomal DNA. Furthermore, multilocus sequence typing classified 97 of 98 members of the pulse type I in the same sequence type (ST), ST-7. Isolates of ST-7 were more toxic to peripheral blood mononuclear cells than ST-1 strains. S. suis ST-7, the causative agent, was a single-locus variant of ST-1 with increased virulence. These findings strongly suggest that ST-7 is an emerging, highly virulent S. suis clone that caused the largest S. suis outbreak ever described.

Animals↗
PubMed2005

Divergence in nonspecific hydrophobic packing interactions in the apo state, and its possible role in functional specialization of mitochondrial and microsomal cytochrome b5.

The outer mitochondrial membrane isoform of mammalian cytochrome b(5) (OM b(5)) is distinguished from the microsomal isoform (Mc b(5)) by its considerably greater stability. In contrast, OM and Mc apocytochrome b(5) (apo-b(5)) exhibit similar thermodynamic stability. Contributing substantially to the greater stability of OM b(5) relative to that of Mc b(5) is the presence of Leu at position 71. Replacing Leu-71 in OM b(5) with the corresponding Mc b(5) residue (Ser) not only diminishes holoprotein stability but also markedly compromises apoprotein stability. The studies reported herein were undertaken to clarify the role played by Leu-71 in stabilizing OM b(5)s relative to Mc b(5)s, and were motivated by the possibility that stability is related to other differences in OM and Mc b(5) properties that are important for their specialized subcellular roles. The results of these studies show that Leu-71 plays an essential role in maintaining the structural integrity of the heme-independent folding core of OM apo-b(5) (core 2), despite its location in the disordered empty heme-binding pocket (core 1). The conformational integrity of core 2 in Mc apo-b(5)s is not similarly dependent on the presence of a hydrophobic residue at position 71, providing new evidence for evolution of compensating structural features not present in OM b(5)s. We propose that Leu-71 achieves its effect on OM apo-b(5) core 2 structure by participating in a nonspecific hydrophobic collapse of disordered core 1, templated by more conformationally restricted side chains of residues in the beta-sheet that separates the two cores. We hypothesize that this has the added effect of maintaining core 1 of OM apo-b(5)s in a state more compact than that which occurs in Mc apo-b(5)s, possibly contributing to stronger heme binding by limiting the number of non-native conformations that the empty heme-binding pocket can populate.

Amino Acid Sequence↗
PubMed2005

Enhancing the stability of microsomal cytochrome b5: a rational approach informed by comparative studies with the outer mitochondrial membrane isoform.

The outer mitochondrial membrane isoform of mammalian cytochrome b5 (OM b5) is much less prone to lose heme than the microsomal isoform (Mc b5), with a conserved difference at position 71 (leucine versus serine) playing a major role. We replaced Ser71 in Mc b5 with Leu, with the prediction that it would retard heme loss by diminishing polypeptide expansion accompanying rupture of the histidine to iron bonds. The strategy was partially successful in that it slowed dissociation of heme from its less stable orientation in bMc b5 (B). Heme dissociation from orientation A was accelerated to a similar extent, however, apparently owing to increased binding pocket dynamic mobility related to steric strain. A second mutation (L32I) guided by results of previous comparative studies of Mc and OM b5s diminished the steric strain, but much greater relief was achieved by replacing heme with iron deuteroporphyrin IX (FeDPIX). Indeed, the stability of the Mc(S71L) b5 FeDPIX complex is similar to that of the FeDPIX complex of OM b5. The results suggest that maximizing heme binding pocket compactness in the apo state is a useful general strategy for increasing the stability of engineered or designed proteins.

Amino Acid Sequence↗
PubMed2005

[Detection of interaction of binding affinity of aromatic hydrocarbon receptor to the specific DNA by exonuclease protection polymerase chain reaction assay].

OBJECTIVE: To establish an exonuclease protection mediated polymerase chain reaction (PCR) assay for the non-radioactive, sensitive detection of the binding of protein and DNA. METHODS: The 1 pmol/L-10 nmol/L 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) dissolved in dimethyl sulphoxide (DMSO), was added into 100 microl SD rat hepatic cytosol in vitro, which contained different amount of aromatic hydrocarbon receptors (AhR) and relative proteins, and ligand-AhR-DRE complex were formed in addition to 1 fmol/L-100 nmol/L DNAs probes containing the sequence of DRE. With the digestion of Exonuclease III and S1 nuclease, free DNAs were digested to oligonucleotide and binding DNA remained due to protein (AhR) protection and be amplified by PCR. The results of PCRs were shown by loading on 2% agarose electrophoresis. DMSO was used as negative control and blank control was set up. RESULTS: Target DNA (285 bp) could be observed in the ligand groups, but not in the control group. The minimal amount of receptor was 2.5 fmol/L and the minimal amount of DNA probes was 2 fmol. CONCLUSIONS: Exonuclease protection mediated PCR assay should be a good non-radioactive tool to quantify the interaction of protein and DNA with high sensitivity and simplicity.

Animals↗
PubMed2004

[The expression of VEGF and iNOS in laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To investigate the mRNA expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) in laryngeal squamous carcinoma and its correlation with clinicopathologic parameters, to identify the interactions between the expression of VEGF and iNOS. METHOD: The mRNA expression of VEGF and iNOS in fresh laryngeal squamous carcinoma tissues and adjacent normal tissues from 40 patients were examined by reverse transcription-polymerase chain reaction. RESULT: The positive expression rate of VEGF and iNOS in tumor samples were significantly higher than that in normal tissues (P < 0.01); in tumor samples, their expression were not associated with age, sex, tumor site and T stage (P > 0.05); their expression were higher in moderately and poorly differentiated tumors than in well differentiated tumors (P < 0.05); their expression were significantly higher in tumors with cervical lymph node metastasis than in tumor without cervical lymph node metastasis (P < 0.01). There were correlation between the expression of VEGF and iNOS in tumor samples (P < 0.05). CONCLUSION: VEGF and iNOS could up-regulate each other to promote the development and cervical lymph node metastasis of laryngeal squamous carcinoma.

Aged↗